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bioRxiv · 10.1101/2025.06.24.661411

Anterior cingulate folding pattern is altered in autism spectrum disorder

Willbrand, E. H.·Maboudian, S. A.·Ludwig, J. J.·Weiner, K. S.
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Abstract

Neuroimaging research has identified focal differences in the cerebral cortex of individuals with autism spectrum disorder (ASD), particularly in the cortical folds (sulci) within higher-level association cortices. The present study investigated the sulcal patterning and morphology of the anterior cingulate cortex (ACC) in individuals with ASD compared to neurotypical (NT) individuals for the first time. We used neuroimaging data from 50 NT and 50 ASD participants. All participants were under 20 years old and male. The two groups were age-matched. Using established criteria and cortical reconstructions generated from each participants T1-weighted magnetic resonance imaging scans with FreeSurfer, we identified the defining sulcal feature of ACC, the variably present paracingulate sulcus (PCGS): its presence in the left and right hemispheres, and asymmetry in PCGS presence between hemispheres. Finally, multiple quantitative morphological features (length, depth, and cortical thickness mean and standard deviation) were extracted from the PCGS using FreeSurfer tools. Analyses revealed that NT participants were more likely to have asymmetrical PCGS patterns than ASD participants (controlling for age and scanner site). However, none of the quantitative morphological features differed between groups. These findings suggest the presence of a variation in the prenatal neurodevelopment of ACC in young males with ASD; however, further research is necessary to uncover the role of this observed difference in the pathogenesis of ASD. The present study also adds to the growing literature implicating variations in PCGS patterning as a trait marker across multiple disorders. Lay SummaryThis study found that young males with autism spectrum disorder (ASD) show less hemispheric asymmetry in the presence of a notoriously variable brain structure (paracingulate sulcus (PCGS)) compared to neurotypical individuals. Considering that this feature of the PCGS develops before birth, the reduced asymmetry may indicate focal differences in brain development in ASD. These findings further enhance our understanding of the neurodevelopmental characteristics of ASD and highlight growing findings indicating that the PCGS may be a useful transdiagnostic marker for various psychiatric conditions.

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Willbrand, E. H., Maboudian, S. A., Ludwig, J. J., Weiner, K. S.. 2025-06-26. Anterior cingulate folding pattern is altered in autism spectrum disorder. https://doi.org/10.1101/2025.06.24.661411

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